2
Indication details
- Control Arm
- SOC (mFOLFOX6 + FOLFOXIRI or CAPOX) ± bevacizumab
- Therapeutic Indication
- Encorafenib with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation.
- Tumour Type
-
Gastrointestinal Cancers
- Tumour Sub-type
- Colorectal cancer
- Tumour Stage
- Metastatic
- Tumour Sub-Group
- BRAF V600E
- Trial Name
- BREAKWATER
- NCT Number
- NCT04607421
- Trial Phase
- Phase III
Approval details
- FDA Approval
- FDA accelerated approval December 2024
Primary Outcome(s)
- Primary Outcome(s)
- RR, PFS (event driven; number of events needed for analysis had not yet been achieved) OS key secondary
- Evaluated Outcome
- RR
- Form(s)
- Form 2c
Outcome Data
- OS Control
- 12 months survival 66%
- OS Gain
- 12 months survival gain 14%
- OS HR
- 0.47 (95% CI: 0.318–0.691; repeated CI: 0.166–1.322). Interim analysis _NS
- RR Gain
- 60.9 % vs. 40%. 20.9% gain
- DoR
- 2.8 months
Adjustments
- QoL Comment
-
QoL data pending
Score (after adjustments)
- Preliminary non-curative score
-
2
- Non-curative score
-
2
Scorecard details
- ESMO-MCBS version
- ESMO-MCBS v1.1
- Scorecard ID
- 489
- Scorecard version
- 1
- Issue date
- 24.02.2025
- Last update
- 26.02.2025
Legend
Information about symbols, abbrevations and color codes
Red = negative
Green = positive
Grey = neutral
?
Grey + ? = neutral with pending data
- DFS
- Disease-Free Survival
- DoR
- Duration of Response
- EFS
- Event-Free Survival
- HR
- Hazard Ratio
- NEB
- No evaluable benefit
- NI
- Non-inferiority Study
- ORR
- Overall Response Rate
- OS
- Overall Surival
- pCR
- Pathological Complete Response/Remission
- PFS
- Progression-Free Survival
- QoL
- Quality of Life
- RFS
- Relapse-Free Survival
- RR
- Response Rate
QoL adjustments
Other adjustments*
Serious and disabling adverse effects
Red = negative / deterioration
Green = positive / improvement
QoL adjustments
Red = negative / deterioration
Green = positive / improvement
Other adjustments*
Red = negative / deterioration
Green = positive / improvement
Serious and disabling adverse effects
Red = negative / deterioration
Green = positive / improvement
* Other adjustments include:
- Long-term plateau in the survival curve
- Long-term plateau in the PFS curve
- Early stopping or crossover
- Only improved PFS mature data shows no OS advantage and no improved Qol.